title: Alpha-actinin 4 and tumorigenesis of breast cancer.
abstract: Alpha-actinins (ACTNs) were originally identified as cytoskeletal proteins which cross-link filamentous actin to establish cytoskeletal architect that protects cells from mechanical stress and controls cell movement. Notably, unlike other ACTNs, alpha-actinin 4 (ACTN4) displays unique characteristics in signaling transduction, nuclear translocation, and gene expression regulation. Initial reports indicated that ACTN4 is part of the breast cancer cell motile apparatus and is highly expressed in the nucleus. These results imply that ACTN4 plays a role in breast cancer tumorigenesis. While several observations in breast cancer and other cancers support this hypothesis, little direct evidence links the tumorigenic phenotype with ACTN4-mediated pathological mechanisms. Recently, several studies have demonstrated that in addition to its role in coordinating cytoskeleton, ACTN4 interacts with signaling mediators, chromatin remodeling factors, and transcription factors including nuclear receptors. Thus, ACTN4 functions as a versatile promoter for breast cancer tumorigenesis and appears to be an ideal drug target for future therapeutic development.
authors.affiliation: Department of Biochemistry, School of Medicine, Case Western Reserve University-CWRU, The Comprehensive Cancer Center of CWRU, Cleveland, Ohio, USA.
authors.forename: Kuo-Sheng
authors.initials: KS
authors.lastname: Hsu
authors.forename: Hung-Ying
authors.initials: HY
authors.lastname: Kao
mesh_terms: D000185:Actinin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D063646:Carcinogenesis; D049109:Cell Proliferation; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D008321:Mammary Glands, Animal / Q000378:metabolism / Q000473:pathology; D042361:Mammary Glands, Human / Q000378:metabolism* / Q000473:pathology; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: C111453:ACTN4 protein, human; D000970:Antineoplastic Agents; D009363:Neoplasm Proteins; D000185:Actinin